Fragility fractures represent a major cause of morbidity in the elderly in the United States and other industrialized countries. These fractures are characterized by their spontaneous or low-energy injury mechanisms, such as falls from standing heights, with mechanical forces that would not ordinarily cause fractures in healthy, young adults. Fragility fractures most commonly occur near the ends of the bone, such as the metaphysis, where there is less cortical bone and more trabecular bone.
Bone's remarkable strength and toughness is due to the nanoscale interaction of the inorganic, mineral portion of the bone material with the organic, collagen portion. Numerous diseases can disturb the mineral portion of the bone, or the collagen portion, or both, all resulting in a bone prone to fracture. In current clinical practice, bone strength and fracture risk associated with disease of the bone is estimated based on evaluation of bone mineral density, while also taking into consideration other factors, such as the patient's age, gender, race, and history of prior fracture. The evaluation of bone mineral density is typically performed by noninvasive means such as dual-energy x-ray absorptiometry (DXA) scans. When appropriate, treatment is available in the form of bisphosphonates, selective estrogen receptor modulators (SERMs), or recombinant parathyroid hormone (PTH) injection.
Unfortunately, the predictive value of an abnormal DXA scan in estimating bone strength and fracture risk is relatively low, particularly with respect to proximal femur fractures, the most morbid of the common fragility fractures. Moreover, when using DXA scans, pathological states involving the organic portion of bone can be underestimated, as only the mineral component of the bone is evaluated.
Additionally, complications of bisphosphonate drug therapy have been highlighted in case series describing an unusual or “atypical” or fatigue fracture thought to be caused by prolonged bisphosphonate treatment. These unique fractures are thought to occur due to a change in a mechanical property of the bone, making the bone less tough and more prone to mechanical fatigue. These “atypical” fatigue fractures occur despite increases in the inorganic or mineral density of bone and again illustrate that measurement of bone mineral density via DXA scan does not provide all the necessary information regarding the material properties of the bone. As the various factors affecting risk of fragility fracture have proven difficult to quantify, a need exists for a more accurate method of predicting this risk.